Policy decisions on endocrine disruptors should be based on science across disciplines: a response to Dietrichet al.

We are writing as scientists and editors of leading peerreviewed journals that have published important contributions in the study of endocrine disrupting chemicals (EDCs). By signing this editorial, we affirm that regulatory decisions on EDCs should be made based on the best available science and expertise that involves, among others, reproductive biology, endocrinology, medicine, genetics, behavior, developmental biology, and toxicology. (For a complete list of Signatories and their Disclosures, see Supplemental Table 1 published on The Endocrine Society’s Journals Online website at http://end. endojournals.org.) Thousands of published studies have revealed the health effects of EDCs on wildlife and laboratory animals and, moreover, have shown associations of EDCs with effects in humans. Many of these studies have been reviewed recently by The Endocrine Society, the United Nations Environment Programme (UNEP), and World Health Organization (WHO), and other independent scientists. The conclusions presented in each of these documents are extraordinarily consistent: like hormones, EDCs are active at very low doses and can induce a range of adverse health outcomes, many of which are not examined in traditional toxicology assays. In sum, these reports point to the conclusion that EDCs pose a global health threat. A recent editorial signed by a number of editors of toxicology journals argues for the status quo in the regulation of EDCs, despite the large volume of evidence indicating that current regulations are ineffective in protecting human populations from these chemicals. As the UNEP/WHO report notes, the incidence of chronic disease is now greater than that of communicable disease; many of these diseases have an endocrine basis. Both experimental animal and epidemiology studies provide plausible causal links between EDCs and many of these diseases; for some, the data are sufficiently robust. The dismissive approach to endocrine disruption science put forth by Dietrich et al. is unfounded, as it is neither based on the fundamental principles of how the endocrine system works and how chemicals can interfere with its normal function, nor does it consider the consequences of that interference. Their letter also ignores a growing and rigorous body of literature on both endogenous hormonal and exogenous EDC effects.

Society News

Gestational diabetes mellitus (GDM) has increased dramatically in the past 20 years together with the obesity epidemic. Mirroring the increase in incidence of GDM is increasing use of endocrine disrupting chemicals (EDCs). EDCs are structurally similar to endogenous hormones and interfere with synthesis, secretion, activity, or elimination of natural hormones, resulting in adverse health effects, including diabetes, obesity, developmental disorders, etc. Although the association between bisphenol A (BPA), a well-studied EDC, and type 2 diabetes has been repeatedly investigated in epidemiological and animal studies, there is a dearth of studies examining EDCs and GDM. In fact, the impact of environmental toxins on perinatal health outcomes has largely been overlooked.Recognizing this research gap, the American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, and International Federation of Gynecology and Obstetrics recently joined leading scientists and clinicians in a call for action to prioritize research in the consequences of exposure to toxic environmental agents on women's health. Evidence is emerging to suggest signaling molecules and EDCs are involved in the control of microRNA (miRNA) expression in trophoblast cells. We reviewed existing scientific evidence of EDCs as a risk factor for GDM as well as the potential role of miRNA in this association.

Moving from awareness to action on preventing patient exposure to toxic environmental chemicals

A new position statement from The Endocrine Society provides a strong argument for scientists in industry, government, and academia to work together, across disciplines, to improve testing of chemicals as potential endocrine disruptors.

On 19 February 2013, the United Nations Environment Programme (UNEP) and the World Health Organization (WHO) released The State of the Science of Endocrine Disrupting Chemicals - 2012 (WHO/UNEP 2013), an extensive update of an earlier document, Global Assessment of the State-of-the-Science of Endocrine Disruptors (International Programme on Chemical Safety 2002). Over the past decade there have been significant advances in our understanding of endocrine disrupting chemicals (EDCs): their numbers, mechanisms of action, biological effects, and impacts on human and wildlife health. First, as described in the new report (WHO/UNEP 2013), the convergence of wildlife, laboratory animal, and epidemiology data suggests a greater role for EDCs in disease, even more than was predicted just 10 years ago. Taking the animal and human evidence together, the report demonstrates a strong likelihood that exposure to EDCs during fetal life and/or puberty plays a role in the proliferation of male and female reproductive problems, endocrine-related cancers, infections, asthma, obesity, diabetes, and behavioral and learning disorders, including attention deficit/hyperactivity disorder (ADHD). The incidences of these conditions have increased significantly not only in the United States but across the globe. Because genes do not change fast enough to explain this increase, environ-mental causes must be involved. The environmental contribution to disease is estimated to be 24–33% of the global disease burden (Smith et al. 1999). Although it is challenging to address the role of the environ-ment in disease, there is also a tremendous opportunity to improve human health by identifying environ-mental elements that affect public health. The recog-nition of these challenges and opportunities, along with the fact that many diseases are associated with the endocrine system (e.g., infertility, diabetes, breast and prostate cancer) has led to the focus on EDCs. Second, it is now accepted that development (in utero and the first years of life) is a very sensitive time for EDC-induced health effects (Kortenkamp et al. 2011). Over the last 10 years, the focus of EDC research has shifted from investigating adult exposure and disease outcomes to examining develop-mental exposure and later-life disease outcomes. This latter approach is now considered the most appropriate approach for most endocrine-related diseases/disorders (U.S. Environmental Protection Agency 2012). Third, identifying those chemicals with endocrine activity from all the chemicals used and released worldwide is a major challenge, and we are likely assessing only the “tip of the iceberg.” Hundreds of chemicals, as well as persistent organic pollutants, have been identified as EDCs. EDCs are not uniform: They have very different properties, sources, and fates in the environment. Although it may be possible to trace high production volume chemicals, numerous additives and process chemicals are not traceable. Adding to this complexity are the unintended and possibly unknown by-products of chemical manu-facturing, including chemicals resulting from combustion, toxicants resulting from the transformation of chemicals after their release into the environment, and internally created metabolites, all of which may increase the number of potential exposures to EDCs in our environment. EDCs likely affect all hormonal systems that control the develop-ment and function of reproductive organs, regulation of metabo-lism, and satiety. Recent research has shown that EDCs also affect physiological systems that control fat develop-ment, weight gain, and glucose levels (Thayer et al. 2012). Finally, as noted in the new WHO/UNEP report (WHO/UNEP 2013), EDCs are a global problem and will require global solutions. EDCs have contaminated the world via the natural flow of air and water. Several hundred EDCs have been measured in humans and wildlife, even in remote places such as the Arctic. Thus, it is now impossible to examine an -unexposed population anywhere on Earth. To improve health, environmental health scientists and toxicologists need to work more closely with colleagues in endocrinology, genetics, developmental biology, epigenetics, and clinical medicine to bring EDC research into the mainstream of science. These and other important topics related to EDCs and their effects are detailed in The State of the Science of Endocrine Disrupting Chemicals - 2012 (WHO/UNEP 2013). I commend WHO/UNEP and the scientists who worked for more than 2 years to produce this report. It is an important source of data on EDCs and should be mandatory reading for everyone who is interested in protecting and improving human health.

To assess the strength of evidence for associations between environmental toxicants and hypertensive disorders of pregnancy, suggest potential biological mechanisms based on animal and in vitro studies, and highlight avenues for future research. Evidence is strongest for links between persistent chemicals, including lead, cadmium, organochlorine pesticides, and polycyclic biphenyls, and preeclampsia, although associations are sometimes not detectable at low-exposure levels. Results have been inconclusive for bisphenols, phthalates, and organophosphates. Biological pathways may include oxidative stress, epigenetic changes, endocrine disruption, and abnormal placental vascularization. Additional prospective epidemiologic studies beginning in the preconception period and extending postpartum are needed to assess the life course trajectory of environmental exposures and women's reproductive and cardiovascular health. Future studies should also consider interactions between chemicals and consider nonlinear associations. These results confirm recommendations by the International Federation of Gynecology and Obstetrics, the American Society for Reproductive Medicine, the American Academy of Pediatrics, and the Endocrine Society that providers counsel their pregnant patients to limit exposure to environmental toxicants.

BUILDING SCIENTIFIC CONSENSUS ON ENDOCRINE DISRUPTORS

AAA award winners.

TORONTO—Twenty-five years after the first baby was conceived through in vitro fertilization (IVF) and nearing the birth of the 2 millionth IVF baby, the longterm health consequences of assisted reproductive technologies have yet to be determined. “There’s been a host of often incomplete and, frankly, very confusing data published on the health of these children,” said Kathy Hudson, PhD, director of the Genetics and Public Policy Center at the Johns Hopkins University, in Washington, DC. Hudson helped enlist a panel of experts to review all of the available data on the health of children conceived through assisted reproductive technologies “to get a better idea of what we know and what we don’t know and to make recommendations for where we need to go next,” she said. The effort was undertaken by Johns Hopkins University in collaboration with the American Academy of Pediatrics and the American Society for Reproductive Medicine. Most of the panel’s findings, presented by Hudson at the annual meeting of the American Society of Human Genetics (ASHG), provide reassurance that these procedures are safe, although there were some areas of concern.

Human Germline Genome Editing

Hormonal changes in humans and animals can be attributed to endocrine disrupting chemicals (EDCs). Studies have found that excessive exposure to natural and artificial environmental chemicals and toxins can have adverse effects on the endocrine system and reproductive health. The endocrine system creates and releases hormones that regulate the development of organs and how they function. Any disruption to hormones affects the development and functioning of the reproductive system, the brain and the neurological system. Research and reports on the subject have been published by international experts and organizations including the World Health Organization (WHO), United Nations Environment Programme (UNEP), International Labour Organization (ILO) and Endocrine Society. To fully comprehend the effect of EDCs on humans and wildlife, it is essential to understand epigenetics and its transgenerational effects on hormone development. Here, we extensively explore and review the research on the sources of EDCs, their effects and why exposure to EDCs is of concern, and treatments for EDC exposure.

IntroductionOver recent decades, controversy regarding standards of care has contributed to questioning past management recommendations for infants and children with a 46,XY DSD. Surveys conducted in 3 waves (2003, 2010, 2020) provide evidence of changes in recommendations for care have changed over this period.MethodsOnline surveys of the members of the Pediatric Endocrine Society (PE) and Societies for Pediatric Urology (PU) included case vignettes representing partial androgen insensitivity syndrome (PAIS), micropenis resulting from primary testicular failure, and penile ablation (non-DSD). Survey items included questions regarding recommended gender of rearing (GoR), genital surgery (and timing), and disclosure of diagnostic details to patient.ResultsThe newborn PAIS vignette included elevated LH and FSH and a 1.2 cm. phallus that increased to 1.7 after exogenous testosterone. Male GoR was chosen by 47, 55 & 55% PE and 81, 83 & 69% of PU in waves 1 to 3, respectively; 27 PE and 28% PU chose an added "non-binary" option in 2020. The recommendation that parents, rather than patients, should decide about perineal hypospadias repair was chosen by 70, 60 & 50% of PE and 93, 90 & 79% of PU. Recommending against surgery were 25, 22 & 10% PE and 23, 13 & 8% PU. Recommending surgery be completed at <1 year of age: 56, 59, 66% PE and 69, 78, 84% PU. Recommendation against disclosure of the underlying condition to the patient 12, 17 & 28% PE and 17, 19 & 22% PU, while 35, 28 to 32% PE and 34, 43 & 30% PU recommended that disclosure occur by 11 years of age. For the penile ablation vignette, 78, 92 & 92% PE and 98, 95 & 97% PU recommended male GoR. The 2020 non-binary option was chosen by 4 and 2% PE and PU. The majority of both groups recommended male GoR for the micropenis vignette with testicular failure; 94, 94 & 89% PE and 96, 97 & 88% PU. The decline in 2020 resulted from the recommendation of the non-binary option by 9% PE and 8% PU.ConclusionsIt seems clear that a female GoR recommendation is currently rare across 46,XY vignettes with evidence of testicular function during at least some of fetal life. It is also apparent that the current emphasis/controversy regarding GoR has resulted in confusion as to how to apply this poorly understood concept. The resulting shift of delaying decisions regarding surgery until the patient can decide is inconsistent with the recommendation that hypospadias repair occur before age 1 year. Finally, lack of or delayed disclosure is inconsistent with patient centered care recommendations.Presentation: No date and time listed

NAS: speaking the truth to power for 150 years

When I invited Elaine Strass for an interview, I had no idea she was planning to retire in the coming year. Elaine has been the hidden force behind both the Genetics Society of America (GSA) and the American Society of Human Genetics (ASHG) for almost 20 years, by serving as Executive Director for both organizations. Fresh, articulate, and cheerful, Elaine (see Image 1) has a lightning wit, great people skills, and zest for her work. She is our societies' strongest champion, yet many of you may be unfamiliar with her.​her.